Process for boron-containing compounds

Abstract

Described herein are boron-containing compounds, compositions, and methods for their preparation.

What is claimed is: 
     
         1 . A process for preparing a compound of Formula (III): 
       
         
           
           
               
               
           
         
         wherein: 
         P 1  is a hydroxyl protecting group; and 
         R a , R b , and R c  are independently hydrogen, fluoro, or chloro; 
         the process comprising reacting a compound of Formula (II) 
       
       
         
           
           
               
               
           
         
          with an oxidizing agent. 
       
     
     
         2 . The process of  claim 1 , wherein the oxidizing agent is potassium permanganate (KMnO 4 ). 
     
     
         3 . The process of  claim 1 , wherein the process further comprises a base. 
     
     
         4 . The process of  claim 1 , wherein the process comprises:
 (i) suspending the compound of Formula (II):   
       
         
           
           
               
               
           
         
          in water; 
         (ii) adding a base to dissolve the compound of Formula (II) in water; 
         (iii) adding an oxidizing agent while stirring; 
         (iv) stirring; 
         (v) adding a solvent to inactivate the excess oxidizing agent; 
         (vi) stirring; 
         (vii) filtering to get a filtrate; 
         (viii) acidifying the filtrate to get a slurry; 
         (viii) cooling the slurry; and 
         (ix) filtering the slurry thereby obtaining the compound of Formula (III): 
       
       
         
           
           
               
               
           
         
       
     
     
         5 . The process of  claim 4 , wherein:
 (a) the base in step (ii) is sodium hydroxide;   (b) the oxidizing agent is potassium permanganate (KMnO 4 );   (c) step (iii) is performed for about 10 h to about 20 h;   (d) the temperature is maintained at between about 20° C. and about 30° C. in step (iii);   (e) the solvent to inactivate the excess oxidizing agent is a primary or secondary alcoholic solvent;   (f) step (vi) is performed for about 10 min to about 2 h;   (g) the filtrate obtained in step (vii) is cooled to between about 0° C. and about 10° C. in step (viii) prior to acidifying;   (h) the acid used for acidifying is sulfuric acid; and/or   (i) the compound of Formula (III) is obtained by filtration.   
     
     
         6 . The process of  claim 1 , wherein the compound of Formula (II): 
       
         
           
           
               
               
           
         
       
       is obtained by reacting a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       with a lithium reagent followed by a borate. 
     
     
         7 . The process of  claim 6 , wherein the compound of Formula (I) is contacted with the lithium reagent to form a compound of Formula (Ia): 
       
         
           
           
               
               
           
         
       
     
     
         8 . The process of  claim 6 , wherein the lithium reagent is n-BuLi. 
     
     
         9 . The process of  claim 6 , wherein the borate is B(OiPr) 3 . 
     
     
         10 . The process of  claim 6 , wherein the process comprises:
 (i) combining a compound of Formula (I):   
       
         
           
           
               
               
           
         
          and a diamine in a solvent; 
         (ii) stirring; 
         (iii) adding a lithium reagent; 
         (iv) stirring; 
         (v) adding a borate; 
         (vi) quenching the reaction by adding an aqueous acidic solution; 
         (vii) separating the layers to obtain an organic layer; 
         (viii) adding an aqueous basic solution to the organic layer; 
         (ix) separating the layers to obtain an aqueous layer; 
         (x) adding an acid to the aqueous layer; 
         (xi) cooling to obtain a suspension; 
         (xii) stirring; 
         (xiii) filtering the suspension, thereby obtaining the compound of Formula (II): 
       
       
         
           
           
               
               
           
         
       
     
     
         11 . The process of  claim 10 , wherein:
 (a) the diamine is TMEDA;   (b) the solvent use in step (i) is cyclohexane;   (c) the lithium reagent is nBuLi;   (d) the borate is B(OiPr) 3 ;   (e) the addition of the lithium reagent in step (iii) is done over about 1 h to about 6 h;   (f) the addition of the lithium reagent in step (iii) is done while the temperature is maintained between about 0° C. and about 20° C.;   (g) step (iv) is performed for about 2 h to about 3 h;   (h) the temperature is cooled to below −70° C. prior to the addition of the borate in step (v);   (i) the temperature is warmed to above −20° C. after to the addition of the borate in step (v);   (j) the aqueous acidic solution in step (vi) is a HCl solution;   (k) the aqueous basic solution in step (viii) is a NaOH solution; and/or   (l) the cooling temperature in step (xi) is about 0° C. and about 5° C.   
     
     
         12 . The process of  claim 1 , further comprising reacting the compound of Formula (III): 
       
         
           
           
               
               
           
         
       
       with (1S,2S,3R,5S)-(+)-pinanediol in a solvent to form a compound of Formula (IV): 
       
         
           
           
               
               
           
         
       
     
     
         13 . The process of  claim 12 , wherein the process comprises:
 (i) mixing the compound of Formula (III), (1S,2S,3R,5S)-(+)-pinanediol, and the solvent;   (ii) heating the resulting mixture;   (iii) cooling to obtain a slurry;   (iv) filtering to obtain the compound of Formula (IV).   
     
     
         14 . The process of  claim 13 , wherein:
 (a) the solvent is n-heptane;   (b) the heating is done to reach reflux;   (c) step (ii) further comprises removing water; and/or   (d) the cooling temperature in step (iii) is below about 60° C.